### UN IT ED STAT E S EN VIRO NM EN TA L P ROT ECT IO N AGENC Y W A S HIN GTO N, D .C. 20 4 60

MEMORANDUM
Date : December 22 , 2014 OFFICE OF CHEM I CA L SA FETY AND POL LUT I ON P REVE NTI ON



### SUBJECT: Paclobutrazol: Respon s e to Re gist rant Comments fro m Syngenta on the Pre liminary Human He alth Ri s k Asses s ment (Septem ber 11 , 2013; DP Barcode: D394230).
PC Code: 1 

### 25601 Decision No.: 486346 Petition No.: NA Risk Assessment Type: NA TXRNo .: NA MRID No.: NA DPBarcode: D417021 Registration No.: 100-1014 Regulatory Action: Registration Review Case No. : 7002 CAS No.: 76738-62-0 40CFR: NA

FROM: Sheila Piper , Risk Assessor

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# ~ lltlf\. Monica H awkins, Ph .D., M.P.H. , Environmental

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# 't? Nancy McCarroll, Ph.D. , Geneticis t/Toxicologist Risk Assessment Branch VI
THROUGH: Donna Davis , Acting Branch

# Chief**~~~** R i s k Assessme nt Branch VI Health Effects Di vision
TO : Khue Nguyen, Chemical Re view Manager Neil Anderson, Branch Chief Risk Management and Implementation Branch I Pesticide Re-evaluation Division (7508 P)

HED ha s received co mments on the review of the pre li mi nary human h ea lth ri sk assessment for Registrat ion Review Septembe r 1 1 , 2013 ; DP Barcode: D394230 (EP A- HQ-OPP-2006-0109- 0021 ).

Page 1 

### of 3EPA's Statement: The studies available for consideration of paclobutrazol toxicity provide a comprehensive database ; however , there are three outstanding studies according to revised 40 CFR Part 158 Toxicology Data Requirement. These studies includ e an acute neurotoxicity (ACN) s tud y, a s ubchronic neurotoxicity (SCN) study , and an immunotoxicity study ( D. Smegal , TXR0056149 , 01 /03 /I2). The registrants have recentl y submitted thefinal A CN study report to the Agency. The Agencyplans to review and inc01porate th e AC N into the revised Registration Review risk assessment. In addition, as specified in the 2012 HASPOC memo, the Agency will reevaluate the need for an SCN based on the results of the ACN. Syngenta's Comment: As noted by the EPA re v iew , Syngenta has submitted an ACN study with paclobutrazol in rats (Rached, 2013; MRID 49148701 ). Based on the lack of evidence of neurotoxicity with paclobutrazol i n the guide li ne ACN study , Syngenta believes that the requirement for a SCN study should be waived. Also, the fu ll database of paclobutrazol, wh ich now include s an ACN s tudy , supports a conclusion that a SCN s tudy would not add to the safety profile of paclobutrazol, and should not be required. Re gard in g the possible need for an immunotoxicity study with paclobutrazol, Syngenta will submit a waiver request , which evaluates the potential for immunotoxicity with paclobutraz ol in accordance with the waiver criteria published by E PA (US EPA , 2013b). This evaluation supports a position that an immunotoxicity study with paclobutrazo1 is not needed , considering the lack of any evidence for effects on the immune syste m in the existing databas e of studies with paclobutrazol.
EPA's Response: The registrant has submitted an acceptable/ guideline ACN stu d y, previously identified as a data gap, and that study has been incorporated into th e most recent risk assessment (D4 1 5247 , Dec X , 2014). In addition, based on the we ight of the evidence (WOE) approach used by HASPOC at th e meeting , which was held February 27 , 2014 , it was recommended that the subchronic neurotoxicity, the subchronic inhalation and the immunotoxicity studies can each be granted data waivers (Leshin, 2014, TXR # 0056914).

EPA's Statement: The restricted entry interval (REI) listed on the exis ting paclobutrazollabels is based on the acute toxicity ofthe technical material. Paclobutrazol is classified as Toxicity Category 1/.for acute dermal toxicity and Toxicity Category JI!.for eye and skin irritation. It is not a dermal sensitizer (Category IV). In accordance with the Worker Protection Standard (WPS) , acute Toxicity Category III and II chemicals require a 24- or 12- hour REI, respectively

. Furthermo re , based on the occupa.tional post-application assessment , most post-application dermal risk estimates do not exceed HED ' s level of concern (MOE s > I 000). Based on the acute derma/toxicity , th e 12 -h our REI that appears on the current paclobutrazollabels may not be adequate and s hould be revisited. Syngenta 's Comment: Syngenta requests that EPA replace the citations and descriptions of older acute toxicity studies fro m 1982 (Appendix A2.1) with the new stud ies submitted in 2012 with the current production source material of paclobutrazol technical. As a result, the wording that discussed results of the older acute dermal toxicity study should be removed, and the final EPA conclusions tha t paclobutrazol is in EPA Toxicity Category III overa ll (signal word Caution) s hou ld be inserted. Therefore, the current Restricted Entry Interval of 12 hours is s upport ed by the acute toxicity data.
Page 2 of3EPA's Response: EP A concurs with Syngenta's comment and will revised the REI recommendat ion in HED's latest rev i sed r is k assessme n t accord i ng l y. EPA's Statement: 

### Residential handler exposures to the existing uses ofpaclobutrazol may occur to adults via the dermal and inhalation route
. All residential handler dermal exposure scenarios do not exceed HED ' s level of concern (MOEs**~I** 

### 000) except for mixing/loading/applyi ng with a belly grinder (MOE= 790). Syngenta's Comment: Syngenta notes that acco rd i ng to the US E PA SO P s , it should be assumed that a product reg i stered for use o n turf gr ass is l ikely to be used on home lawns or by homeown ers u nl ess a spec ific stateme n t on the la b el indicates the p roduct is only to be use d i n non- residential settings. In this case, Syngenta l abe ls for pac lobutrazo l products specifica lly state, 

### ''Do not apply to residential turf" T he refo re, Syngenta respectfu ll y believes thi s statement i s restri ctive enough that resident ial post-app li cation ri sk assessments fo r use sites other than golf co u rses are not necessa r y . T h ere are no granular products in the Syngenta portfolio fo r paclobutrazol, and therefore Syngen ta believes that the be ll y gr inder ap plications are of not of concern. EPA's Response: Paclobutrazo l is not reg i stered for homeowner use on res i de ntial lawns

. A resi d ential hand ler assessme n t was not conducted as part of the revised pacl obutrazo l r is k assessment. A res i den ti al post

- ap plication assessment was pe r forme d as use of paclo b utrazol in parks and go l f courses is expected to res u l t in residenti al post

- ap plication exposure. HED has in cor p orated these changes into HED's latest revised ri sk assessment d ocu me nt (S. P ipe r, 0415247, 12 / 22/20 1 4)

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